Assessment of Rituximab Therapeutic Response Versus Conventional Treatment

Pharmacological Action Clinical Trial

Official title:

Assessment of Rituximab Therapeutic Response Versus Conventional Treatment in the Management of Refractory Nephrotic Syndrome

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05553496
• Other study ID #: PHCL555
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: September 25, 2022
• Est. completion date: October 1, 2023

Study information

• Verified date: September 2022
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective interventional comparative study to compare the efficacy of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome including patients on triple immunosuppression protocols.

Description:

A prospective randomized controlled interventional study, conducted on Refractory Nephrotic syndrome patients with failed different lines of conventional treatment.

The aim of the current study is to assess the therapeutic response of Rituximab versus Conventional treatment in Refractory Nephrotic Syndrome in terms of :

• Improvement in proteinuria.

• Relapse frequency.

Fourty patients with Refractory Nephrotic syndrome will be enrolled in the study. All participants will be previously treated with ACEi and/or ARB, for ≥3 months prior to randomization and adequate blood pressure control. Participants will be assigned randomly into two groups with 20 Refractory Nephrotic syndrome patients in each group as follow:

• Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)

• Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

The duration and severity of proteinuria are known to be surrogate markers of the progression of glomerular disease. Our approach to assess the clinical response was to evaluate estimated Glomerular filtration rate (eGFR), proteinuria and serum albumin after rituximab treatment. We classified the response into four stages :

1. No proteinuria, normal serum albumin

2. Mild proteinuria, serum albumin >30 g/l

3. Ongoing significant proteinuria, serum albumin 20-30 g/l

4. No change in proteinuria and serum albumin. Stages 1 and 2 will be interpreted as a good clinical response, whereas stages 3 and 4 will be interpreted as a poor clinical response.

A sample size of fourty patients with Refractory Nephrotic syndrome is selected to achieve confidence limit of 5%. At the end of the study, a number of data will be generated, such as:

1. Quantitative data will be summarized as means and standard deviations and/or medians and ranges.

2. Categorical data will be summarized as frequencies & percentage.

3. For measuring statistical differences between groups, categorical variables are analyzed using the chi-squared test or Fisher's exact test, whereas continuous variables are compared using Student t tests or Mann-Whitney U tests or Wilcoxon signed-rank test, as appropriate.

4. Statistical comparisons between pre- and post-treatment values are performed using the Wilcoxon signed-rank test.

5. Univariate linear regression models are used to examine the association between baseline characteristics and response to drug treatment.

6. All tests are performed at a significance level of 0.05.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: October 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult = 18 year old and medically stable.

2. Treatment with an Angiotension converting enzyme inhibitor (ACEi) and/or Angiotension II receptor blockade (ARB), for =3 months prior to randomization and adequate blood pressure control or if patient is intolerant to even a very low dose of either ACEi or ARB therapy.

3. Proteinuria =3 g/24 h using the average from two 24-hour urine collections collected within 14 days of each other despite ARB for =3 months as described above.

4. Estimated GFR =40 ml/min/1.73 m2 while taking ACEi/ARB therapy or quantified endogenous creatinine clearance =40 ml/min based on a 24 h urine collection.

5. Non responsive GN patients on conventional treatment.

Exclusion Criteria:

1. Autoimmune diseases.

2. Patients with presence of active infection or a secondary cause of IMN (e.g. hepatitis B, SLE, medications, malignancies).

3. Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy.

4. Pregnancy or breast feeding.

5. Predisposition to drug hypersensitivity.

6. Unstable medical condition.

Related Conditions & MeSH terms

• Pharmacological Action

Intervention

Drug:
• Rituximab
Group (1) RTX in Refractory Nephrotic syndrome patients on conventional treatment (20 patients)
• Dexamethasone
Group (2) Refractory Nephrotic Syndrome patients on Conventional therapy (20 patients)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effectiveness of either conventional therapy alone or Rituximab as an add on therapy will be assessed by measure of Remission sate of the patient.	The primary end point is Complete or Partial remission at 6 months after randomization. Complete remission (CR) is defined as UP =0.3 g/24 h and serum albumin =3.5 g/dl while Partial remission (PR) is defined as Reduction in baseline UP of =50% plus final UP =3.5 g/24 h but >0.3 g/24 h. The patient who will be Non-responsive to therapy is defined as Reduction in baseline UP of <25% (includes increase in UP) after 6 months of immunosuppression and the patient who will enter in the relapsed phase is defined as development of nephrotic range proteinuria following CR or PR, i.e. >3.5 g/24 h.	6 months
Secondary	A) Late Remissions:	The first 6 months of the study will be considered the treatment period, while the remaining 6 months will be considered an observational period.So we will monitor the patients for CR or PR at 6, 9, and 12 months after randomization.	6, 9, and 12 months after randomization.
Secondary	B) Relapse state:	Relapse state of the patient will be assessed at month 12 after randomization (Urine Protein (UP) >3.5 g/24 h after earlier CR or PR).	12 months after randomization
Secondary	C) Response Treatment Time:	The response time will be assessed by measuring the duration of clinical response to RTX in patients who had on going CR or PR.	12 months after randomization
Secondary	D) End Stage Renal Disease (ESRD):	The patients who developed ESRD will be reviewed in this study.	12 months after randomization
Secondary	E) Renal Function:	The effect of treatment on renal function will be assessed every 3 months by calculating the estimated GFR (eGFR) with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula from baseline to 6 months.	6 months after randomization
Secondary	F) Adverse events:	Patients will be educated about adverse effects of the drugs and will be required to report the occurrence of any of them.	6, 9, and 12 months after randomization.